Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210 Shanghai, China.
Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6145-E6151. doi: 10.1073/pnas.1806718115. Epub 2018 Jun 18.
We describe a method for the rapid selection of functional antibodies. The method depends on the cocultivation of that produce phage with target eukaryotic cells in very small volumes. The antibodies on phage induce selectable phenotypes in the target cells, and the nature of the antibody is determined by gene sequencing of the phage genome. To select functional antibodies from the diverse antibody repertoire, we devised a selection platform that contains millions of picoliter-sized droplet ecosystems. In each miniecosystem, the bacteria produce phage displaying unique members of the antibody repertoire. These phage interact only with eukaryotic cells in the same miniecosystem, making phage available directly for activity-based antibody selection in biological systems.
我们描述了一种快速筛选功能性抗体的方法。该方法依赖于在非常小的体积中使产生噬菌体的原核细胞与靶真核细胞共培养。噬菌体上的抗体在靶细胞中诱导可选择的表型，而噬菌体基因组的基因测序决定了抗体的性质。为了从多样化的抗体库中筛选功能性抗体，我们设计了一个选择平台，其中包含数百万个皮升级别的液滴生态系统。在每个微型生态系统中，细菌产生展示抗体库中独特成员的噬菌体。这些噬菌体仅与同一微型生态系统中的真核细胞相互作用，从而使噬菌体可直接用于基于活性的生物系统中的抗体选择。
